RESEARCH SUMMARY. The importance of elucidating the biobehavioral determinants of health disparities in minority populations, and particularly among Mexican immigrants in the U.S., is well established. In this context, an important issue that warrants further investigation relates to the underlying cause(s) of epidemiologic observations that Mexican immigrants exhibit a progressive decline in health (particularly obesity) over time and across generations. The construct of acculturation (post?migration socio?cultural adjustment) is often invoked as an explanation because acculturation produces psychological and behavioral changes that affect health. But, this paradigm does not address intergenerational decline in health. First, I suggest that the intergenerational decline in health (particularly escalation in obesity rates) could be a consequence of acculturation?related biological changes in women. During pregnancy, these changes may be transmitted to the next generation (the fetus) to influence offspring phenotypes that determine susceptibility for obesity (adiposity). A necessary step towards investigating this hypothesis is determining whether, in fact, acculturation is associated with changes in aspects of gestational biology involved in the fetal programming of offspring adiposity. Second, I suggest that many of the inconsistencies of findings across studies in the acculturation?health literatur may relate to limitations of operationalization of the acculturation construct, and failure to consider the role of social context as an effect modifier (context of reception; contrast of life i origin/host countries). My proposal seeks to address both these important limitations. In Project 1 I will develop, in a population?based, representative sample of 1,000 pregnant women, an improved measure of acculturation for Mexican immigrants optimized for health research. In Project 2, in a separate sample of 100 pregnant women, I will evaluate the hypothesis that acculturation status is associated with key indicators of gestational biology implicated in offspring obesity risk. My proposed study incorporates the following Aims: 1. Develop measures of acculturation and socio?cultural context in Mexican immigrant women. 2: Administer and optimize measures of acculturation and socio?cultural context in a representative, population?based cohort of pregnant Mexican immigrant women. 3. Psychometric validation of acculturation and socio?cultural context instruments. 4. Test the hypothesis that acculturation and socio?cultural context are associated with gestational biology (stress and metabolic biomarkers related to fetal programming of obesity). Findings from this project will reveal new information about the health status of vulnerable populations (Mexican immigrants, their unborn children) and serve as a platform for future studies of maternal acculturation and fetal programming, which, in turn, could lead to new avenues for early identification of at?risk individuals, and for prevention/intervention strategies to limit the intergenerational perpetuation of disadvantage and poor health. CANDIDATE SUMMARY. I am primarily interested in the concepts of biological embedding of socio?ecological conditions, and the fetal origins of health and disease paradigm. My career goal is to become an independent investigator in human developmental biology with R01 funding, addressing key questions related to a) how an individual's social and environmental ecology influences biological systems, and b) how biological links between generations affect the development of homeostatic mechanisms associated with chronic disease risk. My short? term career goals are a) to apply the frameworks of evolutionary and developmental biology towards addressing immigrant and minority health, and b) to investigate the socio?cultural effects of migration on gestational biology. My past and current research has been guided by an interest in female reproductive function as a biological continuum between generations, and what this can reveal about health and disease. I was trained in the inter? disciplinary field of Biological Anthropology at Yale University and University of Cambridge. CAREER DEVELOPMENT PLAN SUMMARY. My training plan is designed to allow me to acquire the professional and technical skills necessary for a successful transition to independence as a Human Developmental Biologist with a focus in life?course determinants of chronic disease. I will attain a Master of Science in Biomedical and Translational Science degree during Years 1?2 of the K01 award period. I will be mentored by a team of prominent experts in their respective fields, led by Prof. Pathik Wadhwa (a leader in the field of prenatal stress biology and DOHaD), with co-mentor Prof. Greg Duncan (a leader in the field of development science and member of the National Academy of Sciences) among others, and receive specialized short?term training from a team of distinguished faculty at other universitie, including Prof. John Berry (founder of the field of acculturation studies). ENVIRONMENT SUMMARY. Based in the UC Irvine Development, Health and Disease Research Program (DHDRP), which is currently funded by multiple major NIH grants, I will have myriad resources, including an inter? disciplinary team of 30 senior investigators to provide an intellectually productive environment, research staff, office, and laboratory facilities, and experiential education in state?of?the?art methods for studies of maternal? placental?fetal gestationa biology (including epigenetics, telomere and mitochondrial biology), fetal development, and newborn, infant and child outcomes related to body composition, metabolic function and brain development. The UCI Institute of Clinical and Translational Science (ICTS), funded by the NIH Clinical and Translational Sciences Award (CTSA) program, provides particular support to junior scientists including research design, advanced biostatistics, community engagement, bioassay platforms, and training opportunities, that will directly benefit my training and career development.